Abstract
Our study sets out to show whether vascular endothelial growth factor (VEGF) expression in stage 2B osteosarcomas around the knee influences disease-free and overall survival.
Fifty-two such patients treated in out unit were identified and followed-up for for a minimum of 92 months. All were treated according to the current MRC protocol and had resection of their tumour. Tissue from their resected tumours was stained for VEGF using immunohistochemical methods and the percentage of tumour cells staining for VEGF was assessed. The relationship between VEGF expression and survival was assessed using the log-rank test and Kaplan-Meier survival curves.
At follow-up 32 (62%) patients were dead, all from metastatic disease. Twenty-six (50%) tumours showed expression of VEGF. Statistical analysis showed that patients with tumours with VEGF expression in more than 25% of the cells had significantly shorter overall survival (p=0.019) and disease free intervals (p=0.009). Expression of VEGF also correlated with expression of the proteolytic enzyme MMP9 (p=0.02).
VEGF is peptide which acts as a stimulator of new blood vessel growth in normal tissues, as well as in some solid tumours and their metastases. A tumour which is able to induce a blood supply has an increased ability to grow, seed metastases and threaten life. Our study is the first to look at VEGF expression in the tumour cells surviving after chemotherapy. It is this population of cells which is important as it is these cells which may go on to develop into metastatic or locally recurrent tumours. The over-expression of VEGF by osteosarcoma cells is thought to be associated with a worse prognosis due to a number of mechanisms. This study shows that VEGF expression is an important prognostic factor in osteosarcomas and suggests that the mechanisms by which VEGF and MMP9 expression produce a poor prognosis may be linked. Suppression of tumour angiogenesis by inhibition of the action of VEGF has shown promise in animal models as a potential new treatment for osteosarcoma, and warrants further study.
Theses abstracts were prepared by Professor Roger Lemaire. Correspondence should be addressed to EFORT Central Office, Freihofstrasse 22, CH-8700 Küsnacht, Switzerland.
